首页> 外文期刊>International Journal of Environmental Research and Public Health >L-Asparaginase Isolated from Phaseolus vulgaris Seeds Exhibited Potent Anti-Acute Lymphoblastic Leukemia Effects In-Vitro and Low Immunogenic Properties In-Vivo
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L-Asparaginase Isolated from Phaseolus vulgaris Seeds Exhibited Potent Anti-Acute Lymphoblastic Leukemia Effects In-Vitro and Low Immunogenic Properties In-Vivo

机译:从菜豆种子中分离的L-天冬酰胺酶在体外具有强效抗急性淋巴细胞白血病作用,体内免疫原性低

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Escherichia coli -derived L-asparaginases have been used in the treatment of acute lymphoblastic leukemia (ALL), however, clinical hypersensitivity reactions and silent inactivation due to antibodies against E. coli -asparaginase, lead to inactivation of these preparations in most cases.Therefore, this study was aimed to investigate the cytotoxicity and antitumor effects ofa novel L-asparaginaseenzyme, isolated from Phaseolus vulgaris seeds (P-Asp) on the ALL cell line (Jurkat). The immunogenicity of the enzyme was also evaluated in-vivo and results were compared to commercially available enzymes of microbial sources. The data demonstrated that P-Asp has an enhanced anti-proliferative effect on ALL cells as detected by the WST-8 cell viability assay kit. Cells treated with P-Asp also exhibited a higher degree of early apoptosis compared with asparaginase from Escherichia coli (L-Asp) or its pegylated form Pegasparagas (PEG-ASP) that induced higher rates of late apoptosis and necrosis as detected by an Annexin V/Propidium iodide binding assay. In-vivo experiments indicated that mice treated with P-Asp had less distinct allergenic responses than other bacterial enzyme preparations as indicated by lower serum concentrations of IgG, IgE, IgM and mMCP-1 compared with other treated groups. In conclusion, P-Asp can be considered as a promising candidate for use in the treatment of ALL.
机译:大肠杆菌衍生的L-天冬酰胺酶已被用于治疗急性淋巴细胞白血病(ALL),然而,临床上的超敏反应和抗大肠杆菌-天冬酰胺酶抗体导致的沉默失活在大多数情况下导致这些制剂失活。这项研究的目的是研究从菜豆种子(P-Asp)中分离的新型L-天冬酰胺酶对ALL细胞(Jurkat)的细胞毒性和抗肿瘤作用。还对该酶的免疫原性进行了体内评估,并将结果与​​可商购的微生物来源的酶进行了比较。数据表明,如WST-8细胞活力测定试剂盒所检测,P-Asp对ALL细胞具有增强的抗增殖作用。与P.Asp处理的细胞相比,大肠杆菌(L-Asp)或其聚乙二醇化形式的Pegasparagas(PEG-ASP)的天冬酰胺酶还具有更高程度的早期凋亡,如膜联蛋白V所检测的那样,后者诱导了更高的晚期细胞凋亡和坏死率。 /碘化丙啶结合测定。体内实验表明,与其他治疗组相比,IgG,IgE,IgM和mMCP-1的血清浓度较低,表明用P-Asp处理的小鼠比其他细菌酶制剂的变应原反应要少。总之,可以将P-Asp视为用于ALL治疗的有前途的候选药物。

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